PROJECT SUMMARY In sub-Saharan Africa, infection with malaria parasites during pregnancy is estimated to be the cause of nearly 1 million low birth weight (LBW) babies, 220,000 stillbirths, and 110,000 neonatal deaths every year1-5. Vector control strategies, including long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying of insecticide (IRS) are powerful public health tools for malaria prevention, yet, their current impact on adverse birth outcomes is unknown. LLINs are recommended for all pregnant women in malaria-endemic Africa, but given widespread resistance to the pyrethroid class of insecticide used in LLINs, their efficacy may be waning. An alternative bed net, a pyrethroid-PBO LLIN, shows promise in replacing current LLINs. A recent modeling study showed pyrethroid-PBO LLINs may be highly effective, with the potential to avert up to 500 clinical malaria cases per 1000 person-years compared to standard (i.e. non PBO-treated) LLINs6. To evaluate the public health impact that pyrethroid-PBO LLINs may have for pregnant mothers, epidemiological evidence is needed to augment previous findings from modeling studies. IRS is another important public health strategy shown to be highly effective at reducing the burden of malaria7-12, but has traditionally been under-utilized due to high costs. Exploratory findings from our group suggest IRS is associated with reductions in LBW, preterm birth, and fetal/neonatal death13,14. However, whether IRS is an effective method of preventing malaria- associated adverse birth outcomes requires further evaluation using a more rigorous study design. The goal of this proposal is to investigate the effectiveness of current and new vector-control tools for preventing malaria-associated adverse birth outcomes. Uganda will be used as a case study for this proposal as the recent community distribution of IRS, standard LLINs, and pyrethroid-PBO LLINs provides a unique quasi-experimental opportunity to study these effects. The study will estimate the number of LBW and newborn deaths averted as a direct result of IRS (Aim 1) and standard LLINs (Aim 2a). The study will also assess whether pyrethroid-PBO LLINs confer a greater protective benefit than standard LLINs (Aim 2b). Analyses will use existing data, routinely collected by the Ministry of Health, and rigorous contemporary causal inference methods. The proposal will provide valuable and timely insight on whether existing vector-control strategies are effective or whether new LLINs to should be recommended for use in pregnant women over standard LLINs. Knowledge gained from this research will directly advance the NICHD?s mission of identifying interdisciplinary approaches that will reduce global perinatal deaths. The proposed training, guided by an exemplary mentorship team, will enhance the applicant?s methodological skills, research competency, and content expertise needed for her career as a future independent academic researcher focused on strategies to improve maternal and child health globally.